肿瘤坏死因子抑制剂治疗自身免疫性疾病后炎症性中枢神经系统疾病的风险:系统评价和荟萃分析。
Risk of Inflammatory Central Nervous System Diseases After Tumor Necrosis Factor-Inhibitor Treatment for Autoimmune Diseases: A Systematic Review and Meta-Analysis.
发表日期:2024 Oct 21
作者:
Wenhui Xie, Yunchuang Sun, Wei Zhang, Nanbo Zhu, Shiyu Xiao
来源:
Immunity & Ageing
摘要:
肿瘤坏死因子(TNF)抑制剂已广泛用于治疗各种自身免疫性疾病。然而,关于 TNF 抑制剂治疗后炎症性中枢神经系统 (CNS) 疾病事件的风险,以及这种风险在不同自身免疫性疾病或 TNF 阻断剂之间如何变化的不确定性,目前仍存在争议。 评估炎症性中枢神经系统 (CNS) 风险抗 TNF 治疗后的疾病,并评估不同类型的潜在自身免疫性疾病或 TNF 抑制剂之间的风险差异。从开始到 2024 年 3 月 1 日,在 PubMed、Embase 和 Cochrane 图书馆进行了单独的检索。观察性研究评估了与对照组相比,抗 TNF 治疗和炎症性中枢神经系统疾病。研究资格评估和数据提取由 2 位研究人员按照 PRISMA 指南独立进行。风险比(RR)用作汇总分析的效果衡量标准。主要结局是针对自身免疫性疾病进行抗TNF治疗后发生炎症性CNS事件的风险。根据不同类型的潜在自身免疫性疾病和 TNF 抑制剂进行二次分析。分析了 18 项涉及 1118428 名自身免疫性疾病患者的研究,贡献了超过 5698532 人年的随访。开始使用 TNF 抑制剂后,新发炎症性 CNS 事件的发生率为每 10000 人年 2.0 至 13.4 例。总体而言,与传统疗法相比,暴露于 TNF 抑制剂会导致任何炎症性 CNS 疾病的风险增加 36%(RR,1.36;95% CI,1.01-1.84;I2,49%),主要归因于脱髓鞘疾病(RR,1.36;95% CI,1.01-1.84;I2,49%) 1.38;95% CI,1.04-1.81;I2,31%)。二次分析显示,不同类型的基础自身免疫性疾病的炎症性中枢神经系统疾病风险相似(风湿性疾病:RR,1.36;95% CI,0.84-2.21;炎症性肠病1.49;95% CI,0.93-2.40;亚组 P = .74) 和 TNF 抑制剂(抗 TNF 单克隆抗体与依那西普:RR,1.04;95% CI,0.93-1.15;I2,0%)。与传统疗法相比,暴露于 TNF 抑制剂会导致风险增加 36%炎症性中枢神经系统疾病,无论背景自身免疫性疾病或 TNF 抑制剂类型如何。
Tumor necrosis factor (TNF) inhibitors have been used extensively to treat various autoimmune diseases. However, there are ongoing debates about the risk of inflammatory central nervous system (CNS) disease events following TNF inhibitor therapy, as well as uncertainty about how this risk varies across different autoimmune diseases or TNF-blocking agents.To evaluate the risk of inflammatory CNS diseases after anti-TNF initiation and assess the difference in risk among different types of underlying autoimmune diseases or TNF inhibitors.Separate searches were conducted across PubMed, Embase, and the Cochrane Library from inception until March 1, 2024.Observational studies assessing the association between anti-TNF therapy and inflammatory CNS diseases relative to a comparator group.Study eligibility assessment and data extraction were independently conducted by 2 investigators following PRISMA guidelines. The risk ratio (RR) was used as the effect measure of the pooled analysis.The primary outcome was the risk of incident inflammatory CNS events after anti-TNF therapy for autoimmune diseases. Secondary analyses were performed based on different types of underlying autoimmune diseases and TNF inhibitors.Eighteen studies involving 1 118 428 patients with autoimmune diseases contributing more than 5 698 532 person-years of follow-up were analyzed. The incidence rates of new-onset inflammatory CNS events after initiating TNF inhibitors ranged from 2.0 to 13.4 per 10 000 person-years. Overall, exposure to TNF inhibitors was associated with a 36% increased risk of any inflammatory CNS disease compared to conventional therapies (RR, 1.36; 95% CI, 1.01-1.84; I2, 49%), mainly attributed to demyelinating diseases (RR, 1.38; 95% CI, 1.04-1.81; I2, 31%). Secondary analyses revealed a similar risk of inflammatory CNS diseases across different types of underlying autoimmune diseases (rheumatic diseases: RR, 1.36; 95% CI, 0.84-2.21; inflammatory bowel disease 1.49; 95% CI, 0.93-2.40; P for subgroup = .74) and TNF inhibitors (anti-TNF monoclonal antibodies vs etanercept: RR, 1.04; 95% CI, 0.93-1.15; I2, 0%).Compared to conventional therapies, exposure to TNF inhibitors was associated with a 36% increased risk of inflammatory CNS diseases, irrespective of background autoimmune disease or TNF inhibitor type.